The present invention relates generally to the use of a thin film membrane or coating comprising charged polymers for the separation of optically active or chiral molecules.
The pharmaceutical industry must often produce drugs which are comprised of molecules which are chirally pure (i.e., the molecules are substantially all the same enantiomer). See Stenson, C&EN 45 (May 14, 2001). As such, methods for the commercial-scale separation of chiral forms are highly desirable. Chromatographic methods such as high performance liquid chromatography (HPLC), and supercritical fluid chromatography (SFC) have been used for chiral separation. However, chromatographic methods tend to be slow and labor intensive, and usually require specialized equipment such as simulated moving beds. Chiral separation may also be accomplished using membranes. In contrast to conventional chromatographic methods, chiral separation using one or more membranes offers the advantages of simplicity and higher throughput. Although chiral separation using conventional enantioselective membranes may be considered to be an improvement over conventional chromatographic separation methods, conventional enantioselective membranes are relatively thick (e.g., greater than 1 μm) which tends to reduce the permeation of molecules through the membranes. Additionally, conventional enantioselective membranes are formed by methods such as spray coating, dip coating, plasma polymerization, and chemical grafting which tend to be time consuming, costly, produce membranes which have a relatively high thickness variation, and exhibit low permeability.
Recently, ultrathin polymeric membranes have been prepared using charged polymers, or polyelectrolytes, which are alternately deposited on a substrate or substratum. See Decher and Schlenoff, Eds., Multilayer Thin Films—Sequential Assembly of Nanocomposite Materials, Wiley-VCH, Weinheim (2003); Decher, Science 277, 1232 (1997); and Decher, Hong, and Schmitt, Thin Solid Films 210/211, 831 (1992). For example, a buildup of multilayers may be accomplished by dipping, i.e., cycling a substrate between two reservoirs containing aqueous solutions of polyelectrolytes of opposite charge, with an optional rinse step in pure water following each immersion. Each cycle adds a layer of polymer via electrostatic forces to the oppositely-charged surface and reverses the surface charge thereby priming the film for the addition of the next layer. Films prepared in this manner tend to be uniform, follow the contours and irregularities of the substrate, and are typically between about 10 nm and about 10,000 nm thick. The thickness of a film depends on many factors, including the number of layers deposited, the ionic strength of the solutions, the types of polymers, the deposition time, and the solvent used. Although studies have shown that the substantial interpenetration of the individual polymer layers results in little composition variation over the thickness of a film, such polymer thin films are, nevertheless, referred to as polyelectrolyte multilayers (PEMUs).
Though recently developed, PEMUs are being used in a wide variety of fields including light emitting devices, nonlinear optics, sensors, enzyme active thin films, electrochromics, conductive coatings, patterning, anticorrosion coatings, antistatic coatings, lubricating films, biocompatibilization, dialysis, and as selective membranes for the separation of gaseous and dissolved ionic species. See Fou et al., J. Appl. Phys. 79, 7501 (1996); Decher et al., J. Biosens. Bioelect. 9, 677 (1994); Sun et al., Macromol. Chem. Phys. 197, 147 (1996); Onda et al., Biotech Bioeng 51, 163 (1996); Lvov et al., J. Am. Chem. Soc. 120, 40733 (1998); Laurent et al., Langmuir 13, 1552 (1997); Stepp et al., J. Electrochem. Soc. 144, L155 (1997); Cheung et al., Thin Solid Films 244, 985 (1994); Hammond et al., Macromolecules 28, 7569 (1995); Huck et al., Langmuir 15, 6862 (1999); Stroeve et al., Thin Solid Films 284, 708 (1996); Levasalmi et al., Macromolecules 30, 1752 (1997); Harris et al., Langmuir 16, 2006 (2000); Krasemann et al., 16, 287 (2000); Harris et al., J. Am. Chem. Soc. 121, 1978 (1999); Harris et al., Chem. Mater. 12, 1941 (2000). In fact, PEMUs are particularly suited for use as selective membranes because they are uniform, rugged, easily prepared on a variety of substrates, continuous, resistant to protein adsorption, have reproducible thicknesses, may be made very thin to allow high permeation rates, and may be made from a wide range of compositions. See Graul et al., Anal. Chem. 71, 4007 (1999). In view of the foregoing PEMU attributes, a need exists to develop a method for separating chiral molecules that utilizes enantioselective polyelectrolyte complex membranes.